Directly coaxial 3D bioprinting of large-scale vascularized tissue constructs

Abstract

Three-dimensional (3D) bioprinting of soft large-scale tissues in vitro is still a big challenge due to two limitations, (i) the lack of an effective way to print fine nutrient delivery channels (NDCs) inside the cell-laden structures above the millimetre level; (ii) the need for a feasible strategy to vascularize NDCs. Here, a novel 3D bioprinting method is reported to directly print cell-laden structures with effectively vascularized NDCs. Bioinks with desired tissue cells and endothelial cells (ECs) are separately and simultaneously printed from the outside (mixed with GelMA) and inside (mixed with gelatin) of a coaxial nozzle. As a result, the printed large-scale tissue consists of sheath-core fibers. At the same time, when the core fibers are dissolved to generate channels, the ECs deposit and adhere to the channels automatically. With this method, 3D cell-laden, vascularized tissue constructs (⩾1 cm) with a long-term culture (⩾20 d) are firstly reported. Specifically, vascularized cancer tissue constructs and osteogenic tissue constructs were generated. Considering the above advantages, this advanced bioprinting strategy has significant potential for building large-scale vascularized tissue constructs for applications in tissue engineering, and possibly even in regenerative medicine and organ repair.

Engineering of tissue constructs using coaxial bioprinting

“…Coaxial printing can also aid angiogenesis. Printing of cell-laden sheath and sacrificial or crosslinking core has also been shown to promote vessel-like arrangement and expression of endothelial-specific biomarkers [ 45 , 46 , 62 , 63 ]. Self-arranged lumen structures also emerge from cell migration through homogenous cell-laden core material [ 22 , 28 ] ( Fig.…”

“…Additionally, nutrient exchange within constructs is a formidable barrier. While coaxial bioprinting of vasculature has demonstrated its ability to enable thicker tissue fabrication, these tissues still have relatively small volumes (usually all dimensions are under a centimeter), and future studies will need to continue to push this limit [ 63 ]. Time of fabrication for thick tissues is another key barrier that must be critically addressed, especially for sensitive cells [ 127 ].…”

3D Cell Culture—Can It Be As Popular as 2D Cell Culture?

“…[ 88 ] The filamentous structures, thus, formed can be used for nerve tissue. [ 89 ] Large amounts of fiber can form a film or coating. The scaffold formed by the oriented structure of the filament can also manipulate the cell behavior.…”

Mini-review: advances in 3D bioprinting of vascularized constructs

“…Several research papers exploited this technique [ 27 – 29 ], and Jia et al showed good endothelialization of the hollow channels and a 21-days cell culture under perfusion [ 30 ]. More recently, Shao et al obtained thicker vascularized constructs – up to 1 cm – and were able to combine three coaxial nozzles to yield multicellular tissue matrices [ 31 ]. While the main drawback of coaxial bioprinting is in creating bifurcations, it also shares a hurdle with the other extrusion printing techniques in creating hierarchical networks, since vessels are usually created by a single extrusion of filament.…”